A3 Regulation of antibacterial immune responses in the liver

A03 Mittrücker Foto FP3

Principal Investigator:
Prof. Dr. rer. nat. Hans-Willi Mittrücker
Institut für Immunologie, Diagnostikzentrum
Universitätsklinikum Hamburg Eppendorf
Martinistr. 52
20246 Hamburg
Tel.: +49-40 -7410-57922
Fax: +49-40-7410-54243
E-Mail: h.mittruecker@uke.de

Project description
The liver is a target organ for various pathogens. A bacterial infection leads to the recruitment of neutrophils and monocytes into the liver. For the control of intracellular bacteria, inflammatory monocytes are particularly important. These mature to macrophages, which limit the replication of the bacteria. In addition to macrophages with an anti-bacterial function, there are also macrophages that support tissue regeneration and are referred to as alternatively activated macrophages. The mechanisms of differentiation of monocytes to the different macrophage populations are only insufficiently understood.
The cytokine interleukin-6 (IL-6) supports the control of pathogens and regulates the development of adaptive immune responses. From the previous funding period, there is evidence that IL-6 is also involved in the maturation of monocytes into alternatively activated macrophages. In the current funding period, we will therefore investigate how IL-6 regulates the maturation of alternatively activated macrophages and how this process contributes to the regeneration of liver tissue after infection.

A03 in 60 SecondsVideoarchiv

A03 in 60 Seconds online seit 04.12.2018

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Lücke K, Yan I, Krohn S, Volmari A, Klinge S, Schmid J, Schumacher V, Steinmetz OM, Rose-John S, Mittrücker HW.

Control of Listeria monocytogenes infection requires classical IL-6 signaling in myeloid cells.
PLoS One. 2018 Aug 31;13(8):e0203395. doi: 10.1371/journal.pone.0203395. eCollection 2018.

Rissiek B, Lukowiak M, Raczkowski F, Magnus T, Mittrücker HW, Koch-Nolte F.

In Vivo Blockade of Murine ARTC2.2 During Cell Preparation Preserves the Vitality and Function of Liver Tissue-Resident Memory T Cells.
Front Immunol. 2018 Jul 9;9:1580. doi: 10.3389/fimmu.2018.01580. eCollection 2018.

Dixit A, Bottek J, Beerlage AL, Schuettpelz J, Thiebes S, Brenzel A, Garbers C, Rose-John S, Mittrücker HW, Squire A, Engel DR.

Frontline Science:Proliferation of Ly6C(+) monocytes during urinary tract infections is regulated by IL-6 trans-signaling.
J Leukoc Biol. 2018 Jan;103(1):13-22. doi: 10.1189/jlb.3HI0517-198R. Epub 2017 Dec 28.

Link MA, Lücke K, Schmid J, Schumacher V, Eden T, Rose-John S, Mittrücker HW.

The role of ADAM17 in the T-cell response against bacterial pathogens.
PLoS One. 2017 Sep 6;12(9):e0184320. doi: 10.1371/journal.pone.0184320. eCollection 2017.

Bergmann J, Müller M, Baumann N, Reichert M, Heneweer C, Bolik J, Lücke K, Gruber S, Carambia A, Boretius S, Leuschner I, Becker T, Rabe B, Herkel J, Wunderlich FT, Mittrücker HW, Rose-John S, Schmidt-Arras D

IL-6 trans-signaling is essential for the development of hepatocellular carcinoma in mice
Hepatology. 2017 Jan;65(1):89-103. doi: 10.1002/hep.28874. Epub 2016 Nov 22.

Noll J, Helk E, Fehling H, Bernin H, Marggraff C, Jacobs T, Huber S, Pelczar P, Ernst T, Ittrich H, Otto B, Mittrücker HW, Hölscher C, Tacke F, Bruchhaus I, Tannich E, Lotter H

IL-23 promotes immunopathology and prevents IL-13-dependent tissue repair associated with Ly6C(lo) monocytes in Entamoeba histolytica-induced liver damage
J Hepatol. 2016 May;64(5):1147-57. doi: 10.1016/j.jhep.2016.01.013. Epub 2016 Jan 22.

Wroblewski R, Armaka M, Kondylis V, Pasparakis M, Walczak H, Mittrücker HW, Schramm C, Lohse AW, Kollias G, Ehlken H

Opposing Role of Tumor Necrosis Factor Receptor 1 Signaling in T Cell Mediated Hepatitis and Bacterial Infection In Mice
Hepatology. 2016 Mar 17. doi: 10.1002/hep.28551. [Epub ahead of print]

Through the cleavage of surface proteins, proteases are able to regulate the interaction of cells with cytokines and with other cells. T lymphocytes express the proteases ADAM10 and ADAM17 and for different substrates of these proteases, including the receptors of IL-6 and TNF-α, a function for T lymphocytes has been described. In the current funding period, the role of ADAM10 and ADAM17 in the maturation and function of T cells will be characterized.